What reactions of glycolysis are “irreversible”?
• Note that reactions are irreversible in a physiological sense. • How can reactions become physiologically irreversible when enzymes catalyze fully reversible reactions, and when their catalytic mechanisms are completely reversible? • Product inhibition at [ ] which would allow reasonable reverse flow. • Product KM values do not allow reasonable product binding at physiological concentrations, so minimal catalysis of reverse flow. • Which enzymes are involved in control? • How are regulatory steps determined experimentally? (Keq. vs. measured Q or deltaG). • PFK is the Main regulatory enzyme (flux generating step, first committed step) • Pyruvate Kinase is also regulatory. • Note there are multiple isozymes with differing regulation. Only one form of regulation is discussed below. • PK shows homotropic allosterism towards its substrate, PEP (sigmoidal kinetics). • F-1,6-bisP is a positive effector. • Note that PFK activity also affects PK activity: • If PFK is active F-1,6-bisP builds
